Alcohol-related harm and alcohol consumption in Moscow before, during and after a major anti-alcohol campaign

AIMS: To examine the rates of alcohol-related harm in relation to levels of alcohol consumption before, during and after a major anti-alcohol campaign in Moscow. DESIGN: Changes in State alcohol sale and alcohol consumption and certain forms of alcohol-related harm were observed as a function of time. FINDINGS: Following the 1985 anti-alcohol campaign, State alcohol sales decreased by 38.0% in 1.5 years in Moscow, and total consumption decreased by 28.6%. At the same time, admissions for alcohol-related mental and behavioural disorders, deaths from liver cirrhosis, alcohol poisoning and other blood alcohol positive violent deaths decreased by 63.3%, 33.0%, 50.8% and 50.9%, respectively. There was a linear correlation between medical variables and alcohol consumption during its decrease in 1985-86. An increase in blood alcohol positive violent deaths began in 1987, before the increases in other variables. Growth of total alcohol consumption began in 1987, and continued during all subsequent years, although it was especially high in 1992-93 at the time of the introduction of market reforms in Russia. Alcohol-related mental and behavioural disorders and liver cirrhosis mortality increased after a time-lag following the rise in alcohol consumption. CONCLUSIONS: The findings provide stark evidence of the potential impact of policy measures applied to general alcohol consumption on alcohol-related harm.     

MgADP promotes a catch-like state developed through force-calcium hysteresis in tonic smooth muscle

Tonic rabbit femoral artery and phasic rabbit ileum smooth muscles permeabilized with Triton X-100 were activated either by increasing [Ca2+] from pCa > 8.0 to pCa 6.0 (calcium-ascending protocol) or contracted at pCa 6.0 before lowering [Ca2+] (calcium-descending protocol). The effects of, respectively, high [MgATP]/low [MgADP] [10 mM MgATP + creatine phosphate (CP) + creatine kinase (CK)] or low [MgATP]/[MgADP] (2 mM MgATP, 0 CP, 0 CK) on the "force-[Ca]" relationships were determined. In femoral artery at low, but not at high, [MgATP]/[MgADP] the force and the ratio of stiffness/force at pCa 7.2 were significantly higher under the calcium-descending than calcium-ascending protocols (54% vs. 3% of Po, the force at pCa 6.0) (force hysteresis); the levels of regulatory myosin light chain (MLC20) phosphorylation (9 +/- 2% vs. 10 +/- 2%) and the velocities of unloaded shortening V0 (0.02 +/- 0.004 l/s with both protocols) were not significantly different. No significant force hysteresis was detected in rabbit ileum under either of these experimental conditions. [MgADP], measured in extracts of permeabilized femoral artery strips by two methods, was 130-140 microM during maintained force under the calcium-descending protocol. Exogenous CP (10 mM) applied during the descending protocol reduced endogenous [MgADP] to 46 +/- 10 microM and abolished force hysteresis: residual force at low [Ca2+] was 17 +/- 5% of maximal force. We conclude that the proportion of force-generating nonphosphorylated (AMdp) relative to phosphorylated cross-bridges is higher on the Ca2+-descending than on the Ca2+-ascending force curve in tonic smooth muscle, that this population of positively strained dephosphorylated cross-bridges has a high affinity for MgADP, and that the dephosphorylated AMdp . MgADP state makes a significant contribution to force maintenance at low levels of MLC20 phosphorylation.     

Analysis of the relationship between chimerism and the allgeneic humoral response

BACKGROUND: Persistence of antigens has been suggested to play a role in two opposing immunological phenomena: tolerance and memory. Therefore, we studied the impact of chimerism on alloreactive antibody (allo-Ab) production in kidney transplant patients. METHODS: Thirty-five female renal transplant recipients of male donor organs were classified into the following groups: group 1, 13 sensitized uremic patients on dialysis; group 2, 5 nonsensitized uremic patients on dialysis; group 3, six sensitized patients experiencing graft rejection (3 acute vascular, 1 acute cellular, and 2 chronic); and group 4, 11 nonsensitized with functioning allografts (9 with good function, 1 with acute cellular rejection, and 1 with chronic rejection). Mean duration of dialysis after graft failure was similar in groups 1 (56+/-29.7 months) and 2 (41.8+/-42.4 months), as was dialysis efficiency. Chimerism was measured indirectly in the peripheral blood lymphocytes by polymerase chain reaction amplification of a specific Y chromosome DNA gene sequence with a detection sensitivity limit of 1 male cell per 1 million female cells. Allo-Ab production was measured by the PRA-STAT enzyme-linked immunosorbent assay (Sangstat) method. RESULTS: Chimerism was observed in 60% of groups 1 and 2, 83% of group 3, and 82% of group 4. Among all groups, graft existence, irrespective of its function, positively predicted chimerism in 92% with a sensitivity of 88% and a specificity of 78%. In group 3, all three patients with acute vascular rejection had chimerism and donor-specific allo-Abs. In group 4, eight of the nine patients with no rejection had chimerism. CONCLUSION: Chimerism relates to persistence of allogeneic stimulus irrespective of its function. Chimerism did not confer protection against allo-Ab production or vascular rejection, and its existence was not crucial for sustenance of allo-Ab production.     

Reducing the central porosity of continuous-cast billet by modification of the solidification process

The quality of continuous-cast billet is considered. Means of improving billet solidification are developed, with the pulsed injection of inert gas into the metal in the mold and shear-enhanced mild compression of the billet in the secondary-cooling zone of the continuous-casting machine. These measures are found to shrink the columnar-crystal zone and reduce the central porosity.     

Synthesis and hybridization properties of the conjugates of oligonucleotides and stabilization agents--II

New pyranone derivatives having tri- or pentamethylenamine linker functions were synthesized. These derivatives were covalently attached through the 5'-phosphoramide linkage to heptanucleotide pd(CCAAACA). Complementary complexes of the octanucleotide pd(TGTTTGGC) and above oligonucleotide conjugates were tested for their thermodynamic response. The Tm data and thermodynamic parameters for complex formation have demonstrated the ability of chromone (gamma-pyrone) and coumarin (alpha-pyrone) derivatives to stabilize strongly 7-mer/8-mer complementary complex, most likely through the stacking interaction of the pyran aromatic system with the neighboring nucleotide bases. The effect of chromone (or coumarin) derivatives on the stability of the oligonucleotide complexes (delta delta G at 37 degrees C ranged from -1.0 to -1.7 kcal/mol) was shown to be comparable to the effect of one nucleotide base pair and similar to the effect (delta delta G at 37 degrees C ranged from -1.5 to -2.0 kcal/mol) found for acridineoligonucleotide conjugates served in this study as a reference.     

Use of products made of antimicrobial materials in the prevention of foot mycoses

Field trials were conducted to evaluate effectiveness of mycoses prophylaxis gained by use of antimicrobial insoles and foot-binding with fungicide agents. The trials involved 100 novice soldiers. Bacteriology and bacterioscopy studies diagnosed 47 soldiers as having subclinical mycosis of feet. Using antimicrobial insoles and foot-binding caused considerably lower occurrence of pathogenic fungi in the skin samples; using antimicrobial insoles with regular foot-binding resulted in no changes of the skin microflora. The authors recommend wide application of antimicrobial stuff with fungicide agents for prophylaxis of feet mycosis.     

The gene for progressive myoclonus epilepsy of the Lafora type maps to chromosome 6q

Progressive myoclonus epilepsy of the Lafora type (Lafora's disease) is an autosomal recessive disease characterized by epilepsy, myoclonus, dementia, and periodic acid-Schiff-positive intracellular inclusion bodies. The inclusion deposits consist of branched polysaccharides (polyglucosans) but the responsible biochemical defect has not been identified. Onset is during late childhood or adolescence and the disease leads to a fatal outcome within a decade of first symptoms. We studied nine families in which Lafora's disease had been proven by biopsy in at least one member. In order to locate the responsible gene, we screened the human genome with microsatellite markers spaced an average of 13 cM. We used linkage analysis in all nine families and homozygosity mapping in four consanguineous families to define the Lafora's disease gene region. Two point linkage analysis resulted in a total peak lod score of 10.54 for marker D6S311. Six additional chromosome 6q23-25 microsatellites yielded lod scores ranging from 5.92 to 9.60 at theta m = f = 0. An extended pedigree with five affected members independently proved linkage with peak lod scores over 3.8 at theta m = f = 0 for D6S292, D6S403, and D6S311. The multipoint one-lod-unit support interval covered a 2.5 cM region surrounding D6S403. Homozygosity mapping defined a 17 cM region in chromosome 6q23-25 flanked by D6S292 and D6S420 that contains the Lafora's disease gene.